P53 expression in ischemic rat models after the administration of ketamine and ketamine-xylazine

Ety Sari Handayani, Zainuri Sabta Nugraha, Kuswati Kuswati, Muhammad Yusuf Hisyam, Untung Widodo, Nurul Hidayah, Sahdella Sahdella, Wimpy Wimpy

Abstract


Ketamine and ketamine-xylazine are often used as anesthetic drugs in animal models of ischemia. However, their neuroprotective and neurotoxic effects in ischemic animal models that have undergone tBCCAO are still under debate. The protein p53 is a pro-apoptotic factor involved in the cellular mechanism of ischemia. The interaction between death-associated protein kinase 1 (DAPK 1) and p53 is fundamental in determining whether cells experience necrosis or apoptosis in an ischemic stroke. This study was purposed to identify the presence or absence of differences between the p53 expressions in the brains of tBCCAO-induced ischemic rat models after the administration of ketamine and ketamine-xylazine. It employed a post-test control group design with four groups of adult male Wistar rats as the subject: (1) sham group operated with ketamine, (2) sham group operated with ketamine-xylazine, (3) models of tBCCAO-induced ischemia with ketamine, and (4) models of tBCCAO-induced ischemia with ketamine-xylazine. Ketamine was administered at the dose of 75mg/kg BW, while xylazine was at 8 mg/kg BW. The expression of p53 in rat brains was assessed by semi-quantification, specifically IHC staining with anti-p53 antibodies. P53 expression appeared as brownish stains in the cytoplasm of forebrain pyramidal neurons, and in this study, it was measured using the Allred score. The ANOVA test yielded a p-value of >0.05, implying the absence of difference between the p53 expressions in the brains of tBCCAO-induced ischemic rat models receiving ketamine and ketamine-xylazine.

Keywords


p53;Ketamine Xylazine;tBCCAO

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References


Barbhuiya, A. M., Rahman, H., and Bardalai, D., 2015, Comparative evaluation of various models of ischemic stroke in rats. Scholars Bulletin, 1(2): 38–47.

Fann, D. Y., Lee, S., Manzanero, S., Chunduri, P., Sobey, C. G., and Arumugam, T. V., 2013, Pathogenesis of acute stroke and the role of inflammasomes, Ageing Research Reviews, 12(4): 941–966.

Gonca, E., 2015, Comparison of thiopental and ketamine-xylazine anesthesia in ischemia/reperfusion-induced arrhythmias in rats, Turkish Journal of Medical Sciences, 45(6): 1413–1420.

Handayani, E. S., Nugraha, Z. S., Nurmasitoh, T., Ahsani, D. N., and Nanda, A. G., 2016, Black sugarcane decoction reduces rat brain ischemia, Universa Medicina, 35(1): 40–45.

Handayani, E. S., Nurmasitoh, T., Akhmad, A. S., Fauziah, A. N., Rizani, R., Rahmawaty, Y. R., and Afriandi, A., 2018, Effect of BCCAO duration and animal models sex on brain ischemic volume after 24 hours reperfusion, Bangladesh Journal of Medical Science, 17(01): 129–137.

Helmer, K., Cui, Y., Dewan, A., and Marcer, D., 2003, Ketamine/xylazine attenuates LPS-induced iNOS expression in various rats tissues, The Journal of Surgical Research, 112(1):70–78.

Kaya, A. H., Erdogan, H., and Tasdemiroglu, E., 2016, Searching evidences of stroke in animal models : a review of discrepancies, Turkish Neurosurgery, (Mei), 27(2):1–7.

Kim, S., Cho, K., and Kim, S. Y., 2008, White matter damage and hippocampal neurodegeneration inducedd by permanent bilateral occlusion of common carotid artery in the rat : comparison between wistar and sprague-dawley strain, The Korean Journal of Physiology & Pharmacology, 12(80): 89–94.

Kristin, E., Werner, C., Eva, E., Monika, B., Manfred, B., Eberhard, H., Peter, H., and Eberhard, K., 2003, The effect of the alpha2-agonist dexmedetomidine and the N-Methyl-d-Asapatate Antagonist S(+)-Ketamine on the expression of apoptosis_regulating proteins after incomplete cerebral ischemia and reperfusion in rats, Anesthesia & Analgesia, 96(2): 524–531.

Leffa, D. D., Bristot, B. N., Damiani, A. P., Borges, G. D., Daumann, F., Zambon, G. M., Fagundes, G.E., and de Andrade, V. M., 2015, Anesthetic Ketamine-Induced DNA Damage in Different Cell Types In Vivo, Molecular Neurobiology, 52(3): 1-7.

Lei, H., Grinberg, O., Nwaigwe, C. I., Hou, H. G., Williams, H., Swartz, H. M., and Dunn, J. F., 2001, The effects of ketamine-xylazine anesthesia on cerebral blood flow and oxygenation observed using nuclear magnetic resonance perfusion imaging and electron paramagnetic resonance oximetry, Brain Research, 913(2): 174–179.

Linou, M., Taoufik, E., Kazakos, G., Boviatsis, E., Papadimitriou, L., and Dontas, I. A., 2015, Isoflurane and ketamine / xylazine anesthesia do not Influence the neuroprotective effects of simvastatin in a model ... isoflurane and ketamine / xylazine anesthesia do not influence the neuroprotective effects of simvastatin in a model of permanent cere. British Journal of Medicine & Medical Research, 10(12): 1–12.

Liu, F., Petterson, T., Sadovova, N., Zhang, X., Liu, S., Zou, X., Hanig, J., Paule, M.G., Slikker, W., and Wang, C., 2013, Ketamine-induced neuronal damage and altered n-methyl-d-aspartate receptor function in rat primary forebrain culture, Toxicological Sciences, 131(2): 548–557.

Majid, A., 2014, Neuroprotection in Stroke: Past, Present, and Future, International Scholarly Research Notices, 2014: 1–17.

Mehta, S. L., Manhas, N., and Raghubir, R. 2007, Molecular targets in cerebral ischemia for developing novel therapeutics, Brain Research Reviews, 54: 34–66.

Pei, L., Shang, Y., Jin, H., Wang, S., Wei, N., et al., 2014, DAPK1-p53 Interaction converges necrotic and apoptotic pathways of ischemic neuronal death, Journal of Neuroscience, 34(19):6546–6556.

Prando, S., Carneiro, C. G., Otsuki, D. A., and Sapienza, M. T., 2019, Effects of ketamine/xylazine and isoflurane on rat brain glucose metabolism measure by 18 F-fluorodeoxyglucose-positron emission tomography, European Journal of Neuroscience, 49(1): 51–61.

Rabaglino, M. B., Richards, E. M., Arndt, T. J., Chang, E. I., Miguel, A. Z., Keller-wood, M., and Wood, C. E., 2016, Ketamine decreases inflammatory and immune pathways after transient hypoxia in late gestation fetal cerebral cortex, Physiological Reports, 4(6): 1–15.

Sanderson, T. H., and Wider, J. M., 2013, 2-Vessel occlusion / hypotension : A rat model of global Brain Ischemia, Journal of Visualized Experiments, 76: 1–8.

Traystman, R., 2003, Animal models of focal and global cerebral ischemia, Ilarjournal, 44(2): 85–95.

van der Spuy, W. J., Goosen, D. J., and Bosman, M. C., 2015, Hyperglycemic modification to classical two-vessel occlusion for inducing transient cerebral ischemia in sprague-dawley rats, Journal of Neurophysiology and Neurological Disorders, 2(1): 1–5.

Wang, Y., Liu, G., Hong, D., Chen, F., Ji, X., and Cao, G., 2016, White matter injury in ischemic stroke. Progress in Neurobiology, 141: 45–60.

Yan, J., Huang, Y., Lu, Y., Chen, J., and Jiang, H., 2014, Repeated administration of ketamine can induce hippocampal neurodegeneration and Long-Term cognitive impairment via the ROS / HIF-1 D pathway in developing rats, Cell Physiol Biochem, 2014 (33): 1715–1732.

Zhang, J. Z., Jing, L., Guo, F. Y., Ma, Y., and Wang, Y. L., 2007, Inhibitory effect of ketamine on phosphorylation of the extracellular signal-regulated kinase1/2 following brain ischemia and reperfusion in rats with hyperglycemia. Experimental and Toxicologic Pathology, 59(3-4): 227–235.




DOI: http://dx.doi.org/10.12928/pharmaciana.v10i1.13451

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Pharmaciana
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